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Biomedical subjects

P E Butler

Publications and source records attributed to P E Butler.

At least 19 recordsLinked to original sources

Delayed penile replantation after prolonged warm ischemia.

We report a case of microsurgical replantation of traumatic self-amputation of penis after prolonged warm ischemia as a result of delayed presentation. At 12 weeks postoperative follow-up evaluation, the patient exhibited good urinary flow, spontaneous erection, and a normal response to pharmacological stimulation.

Humans↗

Non-vital, prosthetic, and virtual reality models of microsurgical training.

Many microsurgical training models exist. These can be broadly classified into living and non-living. The latter type can be further sub-classified into non-vital, prosthetic, and virtual reality models. We review each model within these sub-groups with reference to the ideal properties of a training model. The most important attribute of any model is that the skills acquired from it must translate efficiently into microsurgical skill in the clinical situation. We believe that non-vital and prosthetic models are an important complement to living ones in training and maintaining the skills of all microsurgeons. As virtual reality technology improves, virtual models may succeed the rat as the microsurgical training tool of choice.

Clinical Competence↗

Injection of allogeneic bone marrow cells into the portal vein of swine in utero.

The ability to safely manipulate the immune system of the developing fetus carries the hope of effective treatment strategies for certain congenital disorders that can be diagnosed during gestation. One possible intervention is the induction of specific transplantation tolerance to an adult donor who could provide tissue after birth without the need for immunosuppression. Although the introduction of allogeneic stem cells to a developing immune system has been shown to result in hematopoietic chimerism, donor-specific transplantation tolerance has not been demonstrated in a large animal model. In previous reports of in utero stem-cell transplantation, the cells were injected into the fetus by an intraperitoneal route. We sought to improve upon this technique of cell transplantation by developing a method for the safe delivery of allogeneic stem cells directly into the hepatic circulation of fetal swine. In the second phase of our study, we determined if adult allogeneic bone marrow cells delivered to the fetus by this intravascular route could result in result in hematopoietic chimerism and donor-specific transplantation tolerance. A method of successful intravascular injection was designed in which a laparotomy was performed on a sow at midgestation (50-55 days) to administer 1 cc of inoculum into the portal vein of each fetus using transuterine ultrasound guidance and a 25-gauge spinal needle. In one sow, 10 piglets were injected with saline to test safety, and 8 piglets were born. For transplantation of stem cells to the fetuses, donor bone marrow was harvested from a genetically defined miniature swine. In one sow the marrow was injected without T-cell depletion resulting in abortion. In the third sow, the marrow was depleted of T-cells to less than 0.01% using magnetic beads conjugated to anti-CD3 monoclonal antibodies. No chimerism was detected in these offspring. Only in the fourth sow where the T-cell depletion was reduced to about 1% of the cells in the inoculum did one animal demonstrate chimerism. This piglet showed reproducible blood chimerism (0.95% donor cells) detected by flow cytometry measurement of monoclonal antibodies to the donor MHC. In addition, this animal demonstrated hyporesponsiveness to donor lymphocytes in an MLR assay while reacting strongly to third-party stimulator cells. A split-thickness skin graft from the donor was accepted, and a third-party graft was rapidly rejected.

Animals↗

Abdominoplasty wound-healing complications: assisted closure using foam suction dressing.

Abdominoplasty dehiscence, with or without skin necrosis, is a difficult reconstructive problem, which historically entailed protracted management with poor aesthetic outcome. The use of a foam suction dressing in combination with rapid serial wound closure achieves effective delayed primary closure of the abdominoplasty wound with an acceptable aesthetic result. This approach allows effective wound control and functioning, as a mechanical closure device enables rapid closure by serially reducing the foam dressing size with wound closure laterally. This technique has been used in four cases; successful closure was achieved within 8 days, resulting in a stable linear abdominoplasty scar in each case.

Abdominal Muscles↗

Quantitative and qualitative effects of chemical peeling on photo-aged skin: an experimental study.

Chemical peel reverses the visible stigmata of photo aging in human skin. The qualitative and, in particular, the quantitative changes in the dermis that effect this transformation are unclear. This study used a recognized photo-aged animal model, the Skh:HR-1 hairless mouse, to quantify and qualify the changes that occurred in collagen and glycosaminoglycan content after chemical peel. One hundred Skh:HR-1 hairless mice were photo-aged by use of chronic ultraviolet B irradiation for 14 weeks. After irradiation the animals were randomly distributed into five groups of 20 mice each: group 1, control; group 2, 50% glycolic acid peel; group 3, 30% trichloroacetic acid peel; group 4, 50% trichloroacetic acid peel; group 5, phenol peel (Baker-Gordon formula). The respective peeling agent was applied to the dorsal skin of each animal while it was fully anesthetized. Punch biopsies were taken at several times after peel for histological and biochemical analysis. Glycosaminoglycan content was assessed at 14, 28, and 60 days using a colorimetric assay. Collagen content per unit volume increased initially 3 days after the procedure in all chemical peel groups, declining on day 7, and peaking again on day 28. Significant elevations (p < 0.04) were seen in the 30% trichloroacetic acid, 50% trichloroacetic acid, and phenol peels on days 3 and 28 in comparison with controls. This increase in collagen content was not maintained and returned to control values by 60 days. Glycosaminoglycan content per unit volume was elevated initially after peel with significant elevation (p < 0.02) in the 50% trichloroacetic acid and phenol groups on days 14 and 28. This increase in glycosaminoglycan content was not maintained beyond 28 days and declined to control values by day 60 in all groups. Histological examination demonstrated an increase in dermal thickness in the 50% trichloroacetic acid and phenol groups in comparison with controls by day 60. Under polarized light all chemical peel groups at day 60 demonstrated a reorganization of collagen in the reticular and papillary dermis. The elastotic masses that are pathognomonic of photo aging were present in the control group but were absent in the peel groups and demonstrated a reorganization of the elastic fibers in the dermis. This effect was deeper in the dermis in the deeper peel groups (50% trichloroacetic acid and phenol peel). The beneficial effects of chemical peel were due to a combination of two findings; a reorganization in dermal structural elements and an increase in dermal volume. These effects were more pronounced in the deeper peel groups.

Animals↗

Donor modification leads to prolonged survival of limb allografts.

Chronic immunosuppression is essential for maintaining human hand transplant survival because composite tissue allografts are as susceptible to rejection as visceral organ allografts. Limb allografts comprise different types of tissues with varying antigenicities, and the immunosuppressive doses required for these allografts are as high or higher than those required for solid organ allotransplantation. In particular, bone marrow is an early target of the host immune response. This study reports on donor limb modification of the marrow compartment leading to prolonged survival of limb allografts. Chimeric limb allografts comprising a Lewis rat vascularized allograft and Brown Norway rat bone marrow were created. These chimeric limbs were transplanted into three recipients: (1) Buffalo rats (n = 12), where the chimeric limb was allogeneic for both vascular graft and bone marrow; (2) Lewis rats (n = 12), where the limb was allogeneic for marrow alone; and (3) Brown Norway rats (n = 12), where the limb was allogeneic for graft alone. This study found that Brown Norway recipients elicited significantly reduced cell-mediated and humoral immune responses in comparison with the Buffalo and Lewis recipients (p < 0.001 and p < 0.01, respectively). The Buffalo and Lewis recipients both elicited high cell-mediated and humoral responses. The Brown Norway recipients also had prolonged survival of limb tissue allograft in comparison with the other experimental groups.

Animals↗

Leechcraft.

Explore the source record for details and available documents.

Animals↗

Prolonged survival of musculoskeletal xenografts with combined cyclosporine and 15-deoxyspergualin.

This study was undertaken to evaluate the feasibility of performing vascularized musculoskeletal xenografts between mice and rats using immunosuppression. Vascularized musculoskeletal grafts were harvested from the hind limb of C57BL/6J (B6) mice, transplanted heterotopically into Lewis rats, and revascularized by microanastomoses of the graft artery and the recipient femoral artery and the graft vein to the recipient femoral vein. Recipient rats were divided into four groups. Group 1 received no immunosuppression (n = 10), group 2 was treated with cyclosporine (10 mg/kg/day; n = 10), group 3 was treated with 15-deoxyspergualin (5 mg/kg/day; n = 10), and group 4 received both cyclosporine and 15-deoxyspergualin (n = 10). Graft survival was directly examined on postoperative days 4, 7, and 14. In vitro assays were performed using mixed lymphocyte reactions and anti-donor cytotoxic antibody assays to assess the recipient's immune response. Grafts were examined by histology and immunohistochemistry. All grafts in group 1 were rejected by day 4. In groups 2 and 3, all grafts were rejected by day 7. In group 4, however, 8 of 10 recipients had viable grafts on day 14. Data from mixed lymphocyte reactions showed that cell-mediated immune responses were uniformly suppressed in groups 2, 3, and 4 compared with group 1. However, anti-donor antibody production was only partly suppressed in groups 2 and 3, suggesting that graft rejection was primarily caused by circulating cytotoxic anti-donor antibodies in groups 1, 2, and 3. Histologic observations in groups 1, 2, and 3 confirmed the important role of the humoral mechanism in xenograft rejection. Furthermore, immunohistochemical results demonstrated that the small vessels in the rejected grafts showed anti-rat immunoglobulin and complement depositions. Only a combination therapy of cyclosporine and 15-deoxyspergualin attenuated the rejection of xenografts.

Animals↗

Neonatal induction of tolerance to skeletal tissue allografts without immunosuppression.

Vascularized allogeneic skeletal tissue transplantation without the need for host immunosuppression would increase reconstructive options for treating congenital and acquired defects. Because the immune system of a fetus or neonate is immature, it may be possible to induce tolerance to allogeneic skeletal tissues by alloantigen injection during this permissive period. Within 12 hours after birth, 17 neonatal Lewis rats were injected through the superficial temporal vein with 3.5 to 5 million Brown Norway bone marrow cells in 0.1 ml normal saline. Ten weeks after the injection, peripheral blood from the Lewis rats was analyzed for the presence of Brown Norway cells to determine hemopoietic chimerism. The Lewis rats then received a heterotopic, vascularized limb tissue transplant (consisting of the knee, the distal femur, the proximal tibia, and the surrounding muscle on a femoral vascular pedicle) from Brown Norway rat donors to determine their tolerance to the allogeneic tissue. A positive control group (n = 6) consisted of syngeneic transplants from Lewis rats into naive Lewis rats to demonstrate survival of transplants. A negative control group (n = 6) consisted of Brown Norway transplants into naive Lewis rats not receiving bone marrow or other immunosuppressive treatment. The animals were assessed for transplant viability 30 days after transplantation using histologic and bone fluorochrome analysis. All the syngeneic controls (Lewis to Lewis) remained viable throughout the experiment, whereas all the Brown Norway to Lewis controls had rejected. Ten of the 17 allografts transplanted into bone marrow recipients were viable at 30 days, with profuse bleeding from the ends of the bone graft and the surrounding graft muscle. The percent of chimerism correlated with survival, with 3.31 percent (SD = 1.9) of peripheral blood, Brown Norway chimerism present in the prolonged survival groups and 0.75 percent (SD = 0.5) of Brown Norway chimerism in the rejected graft group. This study demonstrated prolonged survival of allogeneic skeletal tissue without immunosuppression after early neonatal injection of allogeneic bone marrow in a rat model.

Animals↗

A comparative study of nerve healing in adult, neonatal, and fetal rabbits.

This experiment quantitatively compared the human equivalent of a nerve repair following surgical division in the fetal, adult, and early childhood period of development using a rabbit as an experimental animal model. Twelve time-dated pregnant New Zealand White rabbits at 24 days' gestation (term = 31 days) underwent hysterotomy; one hind limb was delivered through the uterine opening. The sciatic nerve was divided and repaired by primary neurorrhaphy using two 11-0 epineural sutures. Sciatic nerve repair was also performed in 10 neonatal and 10 adult New Zealand White rabbits. Following repair, each group was assessed using electromyography examination, measuring distal motor latency and amplitude at 1, 2, 3, and 4 months postrepair. There was no difference in any of the groups in distal motor latency. The amplitude rose incrementally in all groups, and the fetal group had significantly higher amplitudes (p < 0.02) at 1, 2, 3, and 4 months in comparison with the adult group. There was no statistically significant difference between fetal and neonatal nerve repairs at any of the time periods. At the completion of the study, the nerve repair sites were harvested for histologic estimation of mean myelinated fiber density and fiber diameter distribution distal and proximal to the repair site. A greater percentage of myelinated axons crossed the repair site in the fetal group (83 percent) in comparison with the adult group (63 percent) (p < 0.03). Our study also demonstrated significant increases in the number of larger myelinated fibers crossing the repair site in comparison with the neonatal and adult groups (p < 0.04). This study found that fetal nerve healing following surgical repair is superior to that found in adult animals and results in a higher number of larger myelinated fibers crossing the repair site in comparison with adult and neonatal repairs.

Aging↗

Effect of early mobilization on healing of nerve repair: histologic observations in a canine model.

The effect of early mobilization on the healing of nerve repair was studied in a canine model. Median and ulnar nerves in the left wrist of 16 adult mongrel dogs were transected and immediately repaired. No motion of the repaired forelimb was allowed in the immobilized group (n = 10), while controlled passive motion between 30 and 90 degrees of wrist flexion was begun on the first postoperative day for 10 minutes twice daily in the mobilized group (n = 6). The pattern of revascularization and collagen formation at neurorrhaphy was examined by transillumination of India ink-injected specimen and by conventional histologic sections. Revascularization of nerve repair was found to occur by ingrowth of capillaries from proximal and distal nerve ends, which typically crossed the neurorrhaphy by 3 weeks in the immobilized group. Following early mobilization, there was a persistent "hypovascular zone" at the nerve repair site for up to 6 weeks. In addition, more scar tissue was generated by early motion according to gross observation and quantitative collagen analysis. Early mobilization, therefore, seems to impede nerve regeneration by delaying revascularization and enhancing scar formation.

Animals↗